Large-vessel involvement in ANCA-associated vasculitis: A multicenter case-control study.

OBJECTIVE: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) primarily affects small vessels. Large-vessel involvement (LVI) is rare. We aimed to describe the characteristics of LVI, to identify associated risk factors, and to describe its therapeutic management. METHODS: This multicenter case-control (1:2) study included patients with AAV according to the ACR/EULAR classification and LVI as defined by the Chapel Hill nomenclature, together with controls matched for age, sex, and AAV type. RESULTS: We included 26 patients, 15 (58 %) of whom were men, with a mean age of 56.0 ± 17.1 years. The patients had granulomatosis with polyangiitis (n = 20), or microscopic polyangiitis (n = 6). The affected vessels included the aorta (n = 18; 69 %) supra-aortic trunks (n = 9; 35 %), lower-limb arteries (n = 5; 19 %), mesenteric arteries (n = 5; 19 %), renal arteries (n = 4; 15 %), and upper-limb arteries (n = 2; 8 %). Imaging showed wall thickening (n = 10; 38 %), perivascular inflammation (n = 8; 31 %), aneurysms (n = 5; 19 %), and stenosis (n = 4; 15 %). Comparisons with the control group revealed that LVI was significantly associated with neurological manifestations (OR=3.23 [95 % CI: 1.11-10.01, p = 0.03]), but not with cardiovascular risk factors (OR=0.70 [95 % CI: 0.23-2.21, p = 0.60]), or AAV relapse (OR=2.01 [95 % CI: 0.70-5.88, p = 0.16]). All patients received corticosteroids, in combination with an immunosuppressant in 24 (92 %), mostly cyclophosphamide (n = 10, 38 %) or rituximab (n = 9, 35 %). CONCLUSION: Regardless of distinctions based on vessel size, clinicians should consider LVI as a potential manifestation of AAV, with the aorta commonly affected. The risk of developing LVI appears to be greater for clinical phenotypes of AAV with neurological involvement. Standard AAV treatment can be used to manage LVI.

FDG PET biomarkers for prediction of survival in metastatic melanoma prior to anti-PD1 immunotherapy.

Our aim was to analyse whether biomarkers extracted from baseline 18F-FDG PET before anti-PD1 treatment contribute to prognostic survival information for early risk stratification in metastatic melanoma. Fifty-six patients, without prior systemic treatment, BRAF wild type, explored using 18F-FDG PET were included retrospectively. Our primary endpoint was overall survival (OS). Total metabolic tumoral volume (MTV) and forty-one IBSI compliant parameters were extracted from PET. Parameters associated with outcome were evaluated by a cox regression model and when significant helped build a prognostic score. Median follow-up was 22.1 months and 21 patients died. Total MTV and long zone emphasis (LZE) correlated with shorter OS and served to define three risk categories for the prognostic score. For low, intermediate and high risk groups, survival rates were respectively 91.1% (IC 95 80-1), 56.1% (IC 95 37.1-85) and 19% (IC 95 0.06-60.2) and hazard ratios were respectively 0.11 (IC 95 0.025-0.46), P = 0.0028, 1.2 (IC 95 0.48-2.8), P = 0.74 and 5.9 (IC 95 2.5-14), P < 0.0001. To conclude, a prognostic score based on total MTV and LZE separated metastatic melanoma patients in 3 categories with dramatically different outcomes. Innovative therapies should be tested in the group with the lowest prognosis score for future clinical trials.

Internal dosimetry through GATE simulations of preclinical radiotherapy using a melanin-targeting ligand.

The GATE Monte Carlo simulation platform based on the Geant4 toolkit is under constant improvement for dosimetric calculations. In this study, we explore its use for the dosimetry of the preclinical targeted radiotherapy of melanoma using a new specific melanin-targeting radiotracer labeled with iodine 131. Calculated absorbed fractions and S values for spheres and murine models (digital and CT-scan-based mouse phantoms) are compared between GATE and EGSnrc Monte Carlo codes considering monoenergetic electrons and the detailed energy spectrum of iodine 131. The behavior of Geant4 standard and low energy models is also tested. Following the different authors' guidelines concerning the parameterization of electron physics models, this study demonstrates an agreement of 1.2% and 1.5% with EGSnrc, respectively, for the calculation of S values for small spheres and mouse phantoms. S values calculated with GATE are then used to compute the dose distribution in organs of interest using the activity distribution in mouse phantoms. This study gives the dosimetric data required for the translation of the new treatment to the clinic.

In vivo experimental imaging of osteochondral defects and their healing using (99m)Tc-NTP 15-5 radiotracer.

PURPOSE: A rabbit model of osteochondral defects (OD) and spontaneous healing was longitudinally followed over 12 weeks, by in vivo joint scintigraphy using (99m)Tc-NTP 15-5, and histology. METHODS: We used two models, one with one OD (OD1 group) in the femoral condyle of one knee and the other with two ODs (OD2 group) in the femoral condyle of one knee, with the contralateral knees serving as the reference. A serial longitudinal imaging study was performed with the scintigraphic ratio (SR, operated knee uptake/contralateral knee uptake) determined at each time-point. RESULTS: ODs were imaged as radioactive defects. The SR was decreased with respective to controls, with values of 0.73 ± 0.08 and 0.65 ± 0.07 in the OD1 and OD2 groups, respectively, at 4 weeks after surgery. Histology of both OD groups revealed the presence of repair tissue characterized by a small amount of sulphated glycosaminoglycans and collagen. CONCLUSION: (99m)Tc-NTP 15-5 imaging provided quantitative criteria useful for in vivo evaluation of cartilage trauma and healing.

[Target volume delineation for head and neck cancer intensity-modulated radiotherapy]. / Délinéation des volumes cibles des cancers des voies aérodigestives supérieures en radiothérapie conformationnelle avec modulation d'intensité

This article describes the determination and the delineation of the target volumes for head-and-neck cancers treated with intensity-modulated radiotherapy (IMRT). The delineation of the clinical target volumes (CTV) on the computerized tomography scanner (CT scan) requires a rigorous methodology due to the complexity of head-and-neck anatomy. The clinical examination with a sketch of pretreatment tumour extension, the surgical and pathological reports and the adequate images (CT scan, magnetic resonance imaging and fluorodeoxyglucose positron emission tomography) are necessary for the delineation. The target volumes depend on the overall strategy: sequential IMRT or simultaneous integrated boost-IMRT (SIB-IMRT). The concept of selectivity of the potential subclinical disease near the primary tumor and the selection of neck nodal targets are described according to the recommendations and the litterature. The planing target volume (PTV), mainly reflecting setup errors (random and systematic), results from a uniform 4-5mm expansion around the CTV. We propose the successive delineation of: (1) the gross volume tumour (GTV); (2) the "high risk" CTV1 around the GTV or including the postoperative tumour bed in case of positive margins or nodal extracapsular spread (65-70 Gy in 30-35 fractions); (3) the CTV2 "intermediate risk" around the CTV1 for SIB-IMRT (59-63 Gy in 30-35 fractions); (4) the "low-risk" CTV3 (54-56 Gy in 30-35 fractions); (5) the PTVs.

Two more cases of evaluation of POEMS syndrome using 18-FDG PET/CT.

Following the article of Alberti et al., we would like to provide our own experience with two more cases in evaluation of POEMS syndrome using morphological and functional imaging modalities, including plain X-rays, computed tomography (CT), magnetic resonance imaging (MRI), bone scintigraphy and positrons emission tomography with computed tomography (PET/CT). Among them, 18-FDG PET/CT proved its usefulness allowing extensive screening of the bony lesions involved.

Intraoperative imprint cytology examination of sentinel lymph nodes after neoadjuvant chemotherapy in breast cancer patients.

BACKGROUND: Intraoperative imprint cytology (IC) is one of several accurate, proven methods to detect tumor cells in sentinel lymph nodes (SLN) from patients with operable breast cancer. In patients treated with neoadjuvant chemotherapy (NAC), studies have demonstrated the feasibility and accuracy of SLN biopsy procedure. We evaluated the validity of IC for SLN testing in patients after NAC. MATERIAL AND METHODS: Patients with infiltrating breast carcinoma receiving NAC (n = 132) were studied prospectively. At surgery, SLN biopsy followed by axillary lymph node dissection was performed. SLN were evaluated using IC in 80 of 132 patients (60%). The results of IC in the adjuvant setting (100 patients) were used for comparison. RESULTS: SLN metastases were correctly identified using IC in 58 of 80 (72%) patients. False negative results were observed in 21 patients. The sensitivity of IC testing was 38.2% and specificity 97.8%. The positive and negative predictive values (PPV and NPV) were 92.9% and 68.2%, respectively. In univariate analysis and multivariate logistic regression analysis, patients with micrometastases or isolated tumor cells in SLN have 2.3 times higher risk of a false negative IC result than patients with macrometastases in SLN (P = .00021; relative risk [RR] = 2.3; 95% confidence interval, 1.37-3.85). The non-NAC group, which contained fewer micrometastatic cases, showed better sensitivity (47.4%) and NPV (88.9%). CONCLUSION: NAC does not seem to influence the accuracy and sensitivity of IC. Variations in sensitivity are related to the proportion of cases with micrometastases and ITC, as it was also shown in chemonaive patients.

Evidence of a clinical response at one yr after reduced-intensity allogeneic hematopoietic stem cell transplantation in heavily pretreated adolescents with aggressive refractory Hodgkin's lymphoma.

We report results of RIC AHSCT in four adolescents with aggressive refractory HL. They all received three or four lines of therapy prior to RIC-AHSCT including autografts. At the time of RIC, they were in partial response except for one patient who had progressive chemoresistant disease. The conditioning regimen consisted of fludarabin, busulfan and ATG. They all had a matched related donor. The median follow-up was 12-16-month post-allograft. All patient transplants engrafted rapidly. The median time of hospitalization was 35 days. The median time to neutrophil recovery (>or=500/muL) was 19 days. All the patients were in complete donor chimerism at day 60. Four patients developed skin (grade

Clinicopathological factors and nomograms predicting nonsentinel lymph node metastases after neoadjuvant chemotherapy in breast cancer patients.

BACKGROUND: Studies have demonstrated the feasibility and accuracy of sentinel lymph node (SLN) biopsy after neoadjuvant chemotherapy (NAC) in breast cancer. Some SLN-positive patients have low risk of nonsentinel lymph node (non-SLN) involvement. Our goal was to determine clinicopathological factors correlating with the presence of non-SLN metastases in patients after NAC and to assess the validity of nomograms predicting additional axillary metastases. METHODS: Patients with infiltrating breast carcinoma (n = 132) were studied prospectively. All patients received NAC. At surgery, SLN biopsy followed by axillary lymph node dissection was performed. Lymphatic mapping was done using the isotope method. Fifty-one patients were SLN positive. RESULTS: In univariate analysis, tumor size (P = 0.016) and the size of SLN metastases (P = 0.0055) were significantly correlated with the presence of non-SLN metastases. In multivariate analysis, SLN macrometastases (P = 0.047) conferred significantly increased risk of non-SLN metastases. The Memorial Sloan-Kettering Cancer Center nomogram was not reliably predictive for non-SLN metastases (area under the receiver operating characteristic curve, AUC, of 0.542), whereas the MD Anderson (AUC 0.716) and Tenon scoring systems (AUC 0.778) were validated. CONCLUSION: Our results suggest that clinicopathological factors predicting non-SLN involvement in SLN-positive patients with and without NAC are essentially the same. The risk of involvement may be assessed using existing nomograms, but additional large prospective studies are needed to determine their accuracy in patients after NAC.

Sentinel lymph node biopsy after neoadjuvant chemotherapy is accurate in breast cancer patients with a clinically negative axillary nodal status at presentation.

BACKGROUND: In breast cancer, neoadjuvant chemotherapy (NAC) is widely used in order to enable a conservative surgery. In patients treated with NAC, the use of sentinel lymph node (SLN) biopsy, which is a good predictor of the axillary nodal status in previously untreated patients, is still discussed. The aim of our study was to determine clinicopathological factors that may influence the accuracy of SLN biopsy after NAC. METHODS: Between March 2001 and December 2006, 129 patients with infiltrating breast carcinoma were studied prospectively. Preoperatively, all of them underwent NAC. At surgery, SLN biopsy followed by axillary lymph node (ALN) dissection was performed. Lymphatic mapping was done using the isotope method. RESULTS: The SLN identification rate was 93.8% (121/129). Fifty-six out of the 121 successfully mapped patients had positive ALN. Eight out of these 56 patients had tumor-free SLN (false-negative rate of 14.3%). The false-negative rate was correlated with larger tumor size (T1-T2 versus T3; P = 0.045) and positive clinical nodal status (N0 versus N1-N2; P = 0.003) before NAC. In particular, the false-negative rate was 0% (0/29) in N0 patients and 29.6% (8/27) in N1-N2 patients. Clinical and pathological responses to NAC did not influence the accuracy of SLN biopsy. CONCLUSION: Our results show that clinical nodal status is the main clinicopathological factor influencing the false-negative rate of SLN biopsy after NAC for breast cancer. SLN biopsy after NAC can predict the ALN status with a high accuracy in patients who are clinically lymph node negative at presentation.